Three randomized, controlled clinical trials have shown that both annual screening and biennial screening for occult blood in the stool significantly reduce the rate of death from colorectal cancer.
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Several observational studies have had similar results.
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The reduction in mortality is evidently a consequence of the earlier detection and surgical removal of malignant colorectal tumors. Fecal occult-blood screening may yield an additional benefit: a reduction in the incidence of colorectal cancer, resulting from the detection and removal of premalignant adenomatous polyps. Fecal occult-blood tests are not very sensitive for the presence of polyps but will detect some, particularly . . .
In 1993 there will be approximately 152,000 new cases of colorectal cancer in the United States and 57,000 deaths from this disease
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. The cause of colorectal cancer is unknown, although ...associations have been reported with family history, diet, alcohol, and sedentary habits
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. In the absence of definitive information to support primary-prevention programs, attention has focused on the use of screening to detect this cancer earlier, when intervention may reduce mortality
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Although the concept of occult-blood detection has existed since 1864, there was little interest in its application to the early detection of large-bowel cancer until 1967, when . . .
BACKGROUND: In 1993, a randomized controlled trial in Minnesota showed, after 13 years of follow-up, that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at ...least 33%. Biennial screening (i.e., every 2 years) resulted in only a 6% mortality reduction. Two European trials (in England andin Denmark) subsequently showed statistically significant 15% and 18% mortality reductions with biennial screening. Herein, we provide updated results —through 18 years of follow-up— from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening. METHODS: From 1976 through 1977, a total of 46 551 study subjects, aged 50-80 years, were recruited and randomly assigned to an annual screen, a biennial screen, or a control group. A screen consisted of six guaiac-impregnated fecal occult blood tests (Hemoccult®) prepared in pairs from each of three consecutive fecal samples. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy. All participants were followed annually to ascertain incident colorectal cancers and deaths. RESULTS: The numbers of deaths from all causes were similar among the three study groups. Cumulative 18-year colorectal cancer mortality was 33% lower in the annual group than in the control group (rate ratio, 0.67; 95% confidence interval CI =0.51-0.83). The biennial group had a 21% lower colorectal cancer mortality rate than the control group (rate ratio, 0.79; 95% CI =0.62-0.97). A marked reduction was also noted in the incidence of Dukes' stage D cancers in both screened groups in comparison with the control group. CONCLUSION: The results from this study, together with the other two published randomized trials of fecal occult blood screening, are consistent in demonstrating a substantial, statistically significant reduction in colorectal cancer mortality from biennial screening.
PURPOSE: To examine the relationships between baseline risk factors and sustained decrease of visual field (SDVF) and sustained decrease of visual acuity (SDVA).
DESIGN: Cohort study of participants ...in the Advanced Glaucoma Intervention Study (AGIS).
METHODS: This multicenter study enrolled patients between 1988 and 1992 and followed them until 2001; 789 eyes of 591 patients with advanced glaucoma were randomly assigned to one of two surgical sequences, argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy (ATT) or trabeculectomy-ALT-trabeculectomy (TAT). This report is based on data from 747 eyes. Eyes were offered the next intervention in the sequence upon failure of the previous intervention. Failure was based on recurrent intraocular pressure elevation, visual field defect, and disk rim criteria. Study visits occurred every 6 months; potential follow-up ranged from 8 to 13 years. For each intervention sequence, Cox multiple regression analyses were used to examine the baseline characteristics for association with two vision outcomes: SDVF and SDVA. The magnitude of the association is measured by the hazard ratio (HR), where HR for binary variables is the relative change in the hazard (or risk) of the outcome in eyes with the factor divided by the hazard in eyes without the factor, and HR for continuous variables is the relative change in the hazard (or risk) of the outcome in eyes with a unit increase in the factor.
RESULTS: Characteristics associated with increased SDVF risk in the ATT sequence are: less baseline visual field defect (hazard ratio HR = 0.86,
P < .001, 95% CI = 0.82–0.90), male gender (HR = 2.23,
P < .001, 1.54–3.23), and worse baseline visual acuity (HR = 0.96,
P = .001, 0.94–0.98); in the TAT sequence: less baseline visual field defect (HR = 0.93,
P = .001, 0.89–0.97) and diabetes (HR = 1.87,
P = .007, 1.18–2.97). Characteristics associated with increased SDVA risk in both treatment sequences are better baseline acuity (ATT: HR = 1.05,
P < .001, 1.02–1.09; TAT: HR = 1.06,
P < .001, 1.03–1.08), older age (ATT: HR = 1.05,
P = .001, 1.02–1.08; TAT: HR = 1.04,
P = .002, 1.01–1.06), and less formal education (ATT: HR = 1.92,
P = .001, 1.29–2.88; TAT: HR = 1.77,
P = .002, 1.22–2.54).
CONCLUSIONS: For SDVF, risk factors were better baseline visual field in both treatment sequences, male gender, and worse baseline visual acuity in the ATT sequence, and diabetes in the TAT sequence. For SDVA, risk factors in both treatment sequences were better baseline visual acuity, older age, and less formal education.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PURPOSE: To investigate the association of pre-intervention and post-intervention patient and eye characteristics with failure of argon laser trabeculoplasty (ALT) and trabeculectomy.
DESIGN: Cohort ...study of participants in the Advanced Glaucoma Intervention Study.
METHODS: This multicenter study took place between 1988 and 2001. Between 1988 and 1992, 789 eyes of 591 patients aged 35 to 80 years with advanced glaucoma were randomized into one of two surgical treatment sequences: argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy or trabeculectomy-ALT-trabeculectomy. Upon study-defined failure (based on maximum medications, sustained intraocular pressure (IOP) elevation, visual field defect, and disk rim deterioration) of each intervention, patients were offered the subsequent intervention. Potential follow-up was 8 to 13 years. This report is based on data from 779 eyes that had at least 3 months of follow-up. The main outcome measures are failure of ALT and trabeculectomy, whether as first or second interventions. Effect size is measured by the hazard ratio (HR) and its corresponding 95% confidence interval (CI) obtained from Cox multiple regression analysis, where HR corresponds to the coefficient of change in risk associated with a unit increase in a factor. For binary factors, this corresponds to the change in risk in eyes with the factor relative to the risk in eyes without the factor.
RESULTS: Pre-intervention factors associated with failure of ALT are younger age (HR = 0.98, CI = 0.96–0.99,
P = .009) and higher IOP (1.11, 1.08–1.15,
P < .001). Pre-intervention factors associated with failure of trabeculectomy are younger age (HR = 0.97, CI = 0.95–0.99,
P = .005) and higher IOP (1.04, 1.01–1.06,
P = .002), as well as diabetes (2.86, 1.88–4.36,
P < .001) and any postoperative complication (1.99, 1.35–2.93,
P < .001). Individual postoperative complications significantly associated with increased risk of failure of trabeculectomy are elevated IOP (3.4, 1.9–6.1,
P < .001) and marked inflammation (2.4, 1.3–4.6,
P = .006).
CONCLUSIONS: In this study, ALT failure was associated with younger age and higher pre-intervention IOP. Trabeculectomy failure was associated with younger age, higher pre-intervention IOP, diabetes, and one or more postoperative complications, particularly elevated IOP and marked inflammation.
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...there has been inadequate evidence of the actual value of this procedure.2 Because of the clinical importance of diabetic retinopathy and the increasing use of photocoagulation in its management, ...the Diabetic Retinopathy Study (DRS) was begun in 1971 under the sponsorship of the National Eye Institute.3 This randomized, controlled clinical trial involves more than 1,700 patients enrolled in 15 medical centers.For this reason, special arrangements have been made for immediate publication of this preliminary report.Because of the necessary stringent limitations of the length of this report, full discussion of study methods and findings will be deferred and only the most essential data presented.When the initially untreated eyes of DRS patients are to be treated, either of the two treatment techniques used in the study is recommended to the ophthalmologist caring for the patient.Since the data do not indicate that focal treatment of NVD or elevated NVE with argon led to better results, adherence to these technically difficult features of the argon treatment protocol will be optional in these eyes.Xenon Group Both Groups Untreated Treated z Value Untreated Treated z Value Untreated Treated z Value A. Cumulative Event Rates Per 100 Eyes at Risk 8 0.9 0.1 2.0 1.7 1.2 0.8 1.3 0.7 1.5 12 3.2 2.0 1.3 4.5 2.7 1.6 3.9 2.4 2.1 16 6.5 3.7 2.0 6.9 3.8 2.2 6.7 3.8 2.9 20 10.6 5.8 2.5 11.0 4.8 3.4 10.8 5.3 4.2 24 15.3 7.4 3.0 17.3 5.3 4.6 16.3 6.4 5.5 28 20.3 7.4 3.8 19.6 5.3 4.8 20.0 6.4 5.9 B. Standard Errors of Difference in Rates of Untreated and Treated Eyes 8 0.4 0.6 0.4 12 0.9 1.1 0.7 16 1.4 1.4 1.0 20 1.9 1.8 1.3 24 2.6 2.6 1.8 28 3.4 3.0 2.3 C. No. of Eyes at Risk in Each Four-Month Interval 4-8 682 682 693 693 1375 1375 8-12 629 632 650 651 1279 1283 12-16 497 500 492 501 989 1001 16-20 394 398 381 392 775 790 20-24 227 237 230 240 457 477 24-28 124 130 113 129 237 259 Table 5 Percentage distribution of change in visual acuity between the pretreatment visit and selected follow-up visits by treatment group Change in Visual Acuity Argon Group Xenon Group Both Groups Untreated Treated Untreated Treated Untreated Treated A. 4 mos Posttreatment (Follow-up visit 2) <= 1 line decrease 88.8 85.1 84.8 73.8 86.8 79.5 2-4 line decrease 6.3 9.8 8.1 17.8 7.2 13.8 >= 5 line decrease but >= 5/200 2.6 3.3 3.4 5.3 3.0 4.3 Visual acuity < 5/200 2.3 1.8 3.8 3.0 3.1 2.4 No. of eyes 766 766 768 768 1534 1534 B. 1 yr Posttreatment (Follow-up visit 4) <= 1 line decrease 77.5 80.2 72.4 71.0 74.9 75.5 2-4 line decrease 8.9 10.2 11.4 18.1 10.2 14.2 >= 5 line decrease but >= 5/200 5.6 3.6 7.7 7.1 6.7 5.4 Visual acuity < 5/200 8.0 6.0 8.6 3.7 8.3 4.9 No. of eyes 550 550 561 562 1111 1112 C. 2 yrs Posttreatment (Follow-up visit 7) <= 1 line decrease 66.3 78.3 63.1 71.5 64.7 74.9 2-4 line decrease 11.4 10.3 9.5 15.6 10.5 13.0 >= 5 line decrease but >= 5/200 7.4 5.7 10.1 8.4 8.8 7.1 Visual acuity < 5/200 14.9 5.7 17.3 4.5 16.1 5.1 No. of eyes 175 175 179 179 354 354 Table 6 Cumulative event rates of visual acuity less than 5/200 at two or more consecutively completed follow-up visits and number of eyes at risk by presence or absence of new vessels based on grading of pretreatment fundus photographs Follow-up, yrs Argon Group Xenon Group Both Groups Untreated Treated z Value Untreated Treated z Value Untreated Treated z Value A. Cumulative Event Rates Per 100 Eyes at Risk∗ a. Eyes with no new vessels 1 0.9 2.1 −0.7 0.0 0.9 −1.0 0.5 1.5 −1.0 2 0.9 3.5 −1.2 3.9 2.0 0.7 2.4 2.7 −0.2 b. Eyes with NVE without NVD 1 0.6 2.4 −1.4 2.2 2.3 −0.1 1.4 2.3 −0.9 2 7.9 5.4 0.7 11.2 3.4 2.0 9.6 4.5 1.9 c. Eyes with NVD with or without NVE 1 5.5 1.6 2.4 7.8 3.4 2.2 6.7 2.5 3.2 2 23.2 10.1 2.9 25.7 6.5 4.3 24.5 8.4 5.0 Follow-up, mos B. No. of Eyes at Risk in Specified Four-Month Intervals† a. Eyes with no new vessels 8-12 114 105 124 130 238 235 20-24 44 36 43 44 87 80 b. Eyes with NVE without NVD 8-12 181 180 180 180 361 360 20-24 66 69 80 71 146 140 c. Eyes with NVD with or without NVE 8-12 262 279 277 270 539 549 20-24 98 112 94 108 192 220 Table 7 Cumulative event rates of visual acuity less than 5/200 at two or more consecutively completed follow-up visits and number of eyes at risk by severity of new vessels and presence of hemorrhage before treatment Follow-up, yrs Argon Group Xenon Group Both Groups Untreated Treated z Value Untreated Treated z Value Untreated Treated z Value A. Cumulative Event Rates Per 100 Eyes at Risk∗ a. Eyes with no new vessels and without hemorrhage 1 0.0 2.3 −1.4 0.0 1.0 −1.0 0.0 1.6 −1.8 2 0.0 3.8 −1.9 4.2 2.1 0.8 2.1 2.9 −0.4 b. Eyes with no new vessels with hemorrhage 1 10.6 0.0 1.0 0.0 0.0 - 5.6 0.0 0.9 2 10.6 0.0 1.0 0.0 0.0 - 5.6 0.0 0.9 c. Eyes with mild NVE without NVD and without hemorrhage 1 0.0 3.7 −1.6 0.0 1.6 −1.1 0.0 2.6 −1.9 2 8.1 3.7 0.8 2.9 1.6 0.4 5.4 2.6 0.9 d. Eyes with mild NVE without NVD with hemorrhage 1 0.0 0.0 - 0.0 0.0 - 0.0 0.0 - 2 0.0 0.0 - 0.0 0.0 - 0.0 0.0 - e. Eyes with moderate or severe NVE without NVD and without hemorrhage 1 1.5 1.3 0.1 1.4 2.3 −0.4 1.5 1.9 −0.3 2 1.5 3.4 −0.7 7.4 4.4 0.6 4.4 4.0 0.1 f. Eyes with moderate or severe NVE without NVD with hemorrhage 1 0.0 4.0 −0.9 8.4 5.7 0.4 5.4 4.7 0.2 2 33.2 18.0 0.8 39.8 5.7 1.8 36.8 13.3 1.8 g. Eyes with mild NVD with or without NVE without hemorrhage 1 1.5 1.6 0.0 0.0 0.0 - 0.7 0.7 0.0 2 14.0 7.1 0.9 5.3 0.0 1.2 9.9 3.0 1.5 h. Eyes with mild NVD with or without NVE with hemorrhage 1 0.0 0.0 - 7.9 0.0 1.3 3.8 0.0 1.3 2 30.5 0.0 1.5 26.0 0.0 1.9 24.0 0.0 2.2 i. Eyes with moderate or severe NVD with or without NVE without hemorrhage 1 6.9 0.0 2.8 5.9 1.0 1.9 6.4 0.5 3.3 2 18.3 9.3 1.4 32.8 3.7 3.6 25.3 6.8 3.7 j. Eyes with moderate or severe NVD with or without NVE with hemorrhage 1 10.4 4.0 1.5 18.5 11.9 1.1 14.8 7.7 1.9 2 41.2 15.9 2.3 35.6 19.3 1.7 38.6 17.5 2.9 Follow-up, mos Argon Group Xenon Group Both Groups Untreated Treated Untreated Treated Untreated Treated B. No. of Eyes at Risk in Specified Four-Month Intervals† a. Eyes with no new vessels and without hemorrhage 8-12 104 96 114 120 218 216 20-24 41 29 39 39 80 68 b. Eyes with no new vessels with hemorrhage 8-12 10 9 10 10 20 19 20-24 3 7 4 5 7 12 c. Eyes with mild NVE without NVD and without hemorrhage 8-12 74 58 69 62 143 120 20-24 20 21 31 20 51 41 d. Eyes with mild NVE without NVD with hemorrhage 8-12 14 15 8 12 22 27 20-24 2 3 4 4 6 7 e. Eyes with moderate or severe NVE without NVD and without hemorrhage 8-12 73 78 73 86 146 164 20-24 37 37 33 39 70 76 f. Eyes with moderate or severe NVE without NVD with hemorrhage 8-12 20 29 30 20 50 49 20-24 7 8 12 8 19 16 g. Eyes with mild NVD with or without NVE without hemorrhage 8-12 73 70 79 85 152 155 20-24 32 25 28 34 60 59 h. Eyes with mild NVD with or without NVE with hemorrhage 8-12 30 23 26 20 56 43 20-24 8 7 9 5 17 12 i. Eyes with moderate or severe NVD with or without NVE without hemorrhage 8-12 103 109 105 100 208 209 20-24 39 56 35 46 74 102 j. Eyes with moderate or severe NVD with or without NVE with hemorrhage 8-12 56 77 67 65 123 142 20-24 19 24 22 23 41 47 1 G. Meyer-Schwickerath, Light-coagulation, Buech Augenarzt, Vol. 33, 1959, 1 2 F. Ederer, R. Hiller, Clinical trials, diabetic retinopathy and photocoagulation, a reanalysis of five studies, Survey Ophthalmol, Vol. 19, 1975, 267 3 Diabetic Retinopathy Study, Letter to Editor, Am J Ophthalmol, Vol. 76, 1973, 403 4 Diabetic Retinopathy Study, Manual of Operations, 1972, Diabetic Retinopathy Study Coordinating Center, Baltimore 5 M.D. Davis, Application of the principles of clinical trials, Am J Ophthalmol, Vol. 79, 1975, 779 6 M.F. Goldberg, S.L. Fine, Symposium on the Treatment of Diabetic Retinopathy, U.S.P.H.S. publication No. 1890, 1969, U.S. Government Printing Office, chapter 2 7 A.S. Littell, Estimation of the T-year survival rate from follow-up studies over a limited period of time, Hum Biol, Vol. 24, 1952, 87
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We developed a Dry Eye Screening Questionnaire for the Dry Eye Epidemiology Projects (DEEP), a proposed large epidemiologic study. All persons who screen positive and a small sample of those who ...screen negative are to be invited for a diagnostic examination. Containing 19 questions, of which only 14 were used in the analysis, the questionnaire takes only a few minutes to administer on the telephone. To construct a discriminator function and thus a ROC curve, we used stepwise multiple regression on screening responses from a clinic series of 77 cases and 79 controls. Stepwise regression may incorporate into the predictor equation variables whose relation to the predicted is only accidental. Further, misclassification rates are underestimated by the resubstitution method, in which the proportion misclassified is obtained from the same dataset in which the discriminator function was fitted. To counter these problems, we randomly divided the data in half. We chose as predictors only those variables (Dry and Irritated) selected by stepwise regression in both data halves. We estimated unbiased misclassification rates using the unbiased test set method, in which the discriminator is fitted in one data half, and misclassification rates are calculated in the other half. Comparison of ROC curves arising from resubstitution and test set estimates indicates that resubstitution bias in misclassification rate estimation is negligible in our data. A resubstitution estimate made on the entire data is thus preferred. The resulting sensitivity/specificity values are reasonably high (e.g., 60%/94%), suggesting that the questionnaire will be a useful screening tool in the DEEP study. A second discriminator using the sum of all 14 responses is similar in its misclassification characteristics to the first discriminator. A second potentially significant error, arising from applying results from a clinical series to a general population, will be investigated as survey results in DEEP become available.
To determine the least worsening of a visual field (VF) and the least number of confirming tests needed to identify progression of glaucomatous VF defects.
Cohort study of participants in a clinical ...trial.
Seven hundred fifty-two eyes of 565 patients with advanced glaucoma.
Visual field tests were quantified with the Advanced Glaucoma Intervention Study (AGIS) VF defect score and the Humphrey Field Analyzer mean deviation (MD). Follow-up was 8 to 13 years.
Two measures based on the AGIS VF defect score: (1) sustained decrease of VF (SDVF), a worsening from baseline by 2 (alternatively, 3 or 4) or more units and sustained for 2 (alternatively, 3) consecutive 6-month visits and (2) after the occurrence of SDVF, the average percent of eyes with worsening by 2 (alternatively, 3 or 4) or more units from baseline. Two similar measures based on MD.
Based on the original AGIS criteria for SDVF (a worsening of 4 units in the AGIS score sustained during 3 consecutive 6-month visits), 31% of eyes had an SDVF. The percent of eyes with a sustained event increases by approximately 10% when either the minimum number of units of field loss or the minimum number of 6-month visits during which the loss is sustained decreases by 1. During 3 years of follow-up after a sustained event, a worsening of at least 2 units was found in 72% of eyes that had a 2-visit sustained event. The same worsening was found in 84% of eyes that had a 3-visit sustained event. Through the next 10 years after a sustained event, based on worsening of 2, 3, or 4 units at 2 or 3 consecutive tests, the loss reoccurred, on average, in >/=75% of study eyes. Results for MD are similar.
In patients with advanced glaucoma, a single confirmatory test 6 months after a VF worsening indicates with at least 72% probability a persistent defect when the worsening is defined by at least 2 units of AGIS score or by at least 2 decibels of MD. When the number of confirmatory tests is increased from 1 to 2, the percentage of eyes that show a persistent defect increases from 72% to 84%.
In the Minnesota Colon Cancer Control Study, which used guaiac slides to annually screen stool samples for blood, mortality from colorectal cancer was reduced by 33.4%. The reported sensitivity of ...this test for colorectal cancer was about 90%. However, results from another study estimated the sensitivity to be 25%-33%; other investigators have reported intermediate values. Given these contradictions, we examined screening sensitivity for colorectal cancer in the Minnesota study by several direct and indirect methods.
In this reanalysis of data from the Minnesota study, we distinguished between sensitivity for colorectal cancer of the screening test (composed of six slides) and of the screening program (a series of such tests). We estimated screen sensitivity by adjusting the crude estimate from the final tests in each screening phase for colorectal cancer incidence in 5 years of follow-up, by modeling guaiac slide results at each screen as a function of the presence of occult blood, and by incorporating sensitive detection into a modification of a mathematical model developed by Lang and Ransohoff. Program sensitivity was estimated from the fraction of screen-detected cancers among all cancers diagnosed in screened individuals.
The crude estimate of program sensitivity was 89.4%, whereas the modified Lang-Ransohoff model estimates screen sensitivities at 94.1%-96.2%, consistent with the estimates from the other methods. Indirect measures, such as the association between the number of positive slides among the six slides in each set and the positive predictivity for colorectal cancer, are consistent with these estimates.
The Minnesota study reduced mortality from colorectal cancer through use of a screening test with average screen and program sensitivities of about 90%.
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